"The neural hallmarks of psychosis are increased presynaptic striatal dopamine function1 and structural and functional abnormalities in the hippocampus.
Both elevated striatal dopamine function and hippocampal abnormalities are also evident in subjects at ultra high risk (UHR) for psychosis,
suggesting that they are associated with an increased vulnerability for psychosis.
Animal models of psychosis propose that these two abnormalities may be linked via a polysynaptic pathway involving the hippocampus, basal ganglia and midbrain.7, 8 Cognitive models of psychosis propose that psychotic symptoms develop as a result of altered salience processing
Taken together, these models propose that the presence of a salient stimulus in healthy subjects is associated with increased hippocampal activity and descending glutamatergic drive to GABAergic neurons in the ventral striatum. This suppresses the activity of GABAergic neurons in the ventral pallidum that normally inhibit the activity of dopaminergic neurones in the midbrain. Dopamine function is thus enhanced by salient stimuli and this hippocampal–basal ganglia–midbrain loop is thought to mediate the attribution of salience to environmental signals based on the context.
In patients with psychosis, it is suggested that resting overactivity in the ventral hippocampus drives the ventral striatum to potently inhibit the ventral pallidum, markedly increasing the number of spontaneously active midbrain dopamine neurons, and leading to an increase in dopaminergic activity that is uncoupled from context. Data from multimodal neuroimaging studies in UHR individuals are consistent with this model, indicating that the relationship between hippocampal activity and glutamate levels with striatal dopamine function is significantly altered compared to that in controls..
The aberrant salience hypothesis of psychosis proposes that chaotic dopamine release can perturb salience processing in two ways.
If phasic dopamine release is dysregulated and coincides with the processing of stimuli that would normally be irrelevant, these may become inappropriately salient. Conversely, if the phasic dopamine release that normally occurs in response to contextually relevant cues is impaired, stimuli that would normally be salient may become less so. This is consistent with data from recent studies in UHR subjects and in patients with psychosis, which report impairments in both forms of salience processing"
Hippocampus activity during Conrad's Trema stage of progress into
anxiety and schizophrenia
A broad range of neural and behavioral data suggests that the brain contains multiple systems for behavioral choice, including one associated with prefrontal cortex and another with dorsolateral striatum. However, such a surfeit of control raises an additional choice problem: how to arbitrate between the systems when they disagree.
Here, we consider dual-action choice systems from a normative perspective, using the computational theory of reinforcement learning. We identify a key trade-off pitting computational simplicity against the flexible and statistically efficient use of experience. The trade-off is realized in a competition between the dorsolateral striatal and prefrontal systems. We suggest a Bayesian principle of arbitration between them according to uncertainty, so each controller is deployed when it should be most accurate. This provides a unifying account of a wealth of experimental evidence about the factors favoring dominance by either system.
Striatum :reward and threat
hippo str together
Menegas et al. demonstrate a role for midbrain dopamine neurons projecting to the tail of the striatum in encoding stimulus novelty and threat avoidance. From this study emerges a model whereby distinct dopaminergic projections to striatum influence behavior along at least two axes, one representing value and one representing thrreatening stimuli
Midbrain dopamine neurons are well known for their role in reward-based reinforcement learning. We found that the activity of dopamine axons in the posterior tail of the striatum (TS) scaled with the novelty and intensity of external stimuli, but did not encode reward value. We demonstrated that the ablation of TS-projecting dopamine neurons specifically inhibited avoidance of novel or high-intensity stimuli without affecting animals’ initial avoidance responses, suggesting a role in reinforcement rather than simply in avoidance itself. Furthermore, we found that animals avoided optogenetic activation of dopamine axons in TS during a choice task and that this stimulation could partially reinstate avoidance of a familiar object. These results suggest that TS-projecting dopamine neurons reinforce avoidance of threatening stimuli. More generally, our results indicate that there are at least two axes of reinforcement learning using dopamine in the striatum: one based on value and one based on external threat.
striatal memory route
The striatum/putamen stream decides where incoming stimuli carrying information are
given their priority and significance.
brain cellmapping indicates activity in the striatum may predict schizophrenia
" During psychosis, coherent intrinsic activity of the striatum was increased
in the dorsal part and correlated with positive symptoms such as delusion and
In psychotic remission of the same patients, activity of the
ventral striatum was increased and correlated with negative symptoms such as
emotional withdrawal and blunted affect"
There are two routes in the brain which store away long term memories of
useful experience for later use. They take different starting points and end
up with a different entry to the store.
In the hippocampus neurogenesis - continual new cells being made -deals with
new intake stuff, neorogenesis ability being an essential part of deciding
what of the new will be accepted into updating memory store., ensuring what's
been taken in is able to be recalled , is consciously wanted for whatever lies
ahead in the day, in the week.
When hippocampal new cell formation is reduced, memory for sorting what is new
and relevant is lost: memory for manipulating what is stored is impaired.
Declarative memory (“knowing what”) is memory of facts and events, and refers
to those memories that can be consciously recalled (or "declared"). It is
sometimes called explicit memory, since it consists of information that is
explicitly stored and retrieved, although it is more properly a subset of
explicit memory. Declarative memory can be further sub-divided into episodic
and semantic memory
The other route which is now known to have continual cells - neurogenesis
[Ernst et al ] - a new cell production line is through the striatum Its memory
is in a separate place, where unconsciously action is available. If the
striatum is destroyed the procedural storing is lost. riding the bicycle that
had become automatic could not be learnt.
Hippocampal new cell failure brings 'cognitive' failure. Manipulating thoughts
that keep upwith daily coping and looking ahead, becomes uncertain , often
Striatal failure means procedural memory - Procedural memory (“knowing how”)
is the below conscious memory of skills and how to do things: talking. walking,
particularly the use of objects or movements of the body, such as tying a
shoelace, playing a guitar or riding a bike.
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